Section: Research

Aldo Rossini, M.D.

Academic Role: Professor

Faculty Appointment(s) In:
   Diabetes
   Medicine

Other Affiliation(s):
   Center for AIDS Research
   Clinical and Population Health Research
   Interdisciplinary Graduate Program
   Program in Immunology and Virology

Diabetes Research

The goal of our research is to understand the mechanisms of tolerance as they apply to 1) the pathogenesis of autoimmune insulin-dependent (Type I) diabetes mellitus and 2) its cure by pancreatic islet transplantation. Type I diabetes occurs when ‘auto reactive immune cells, which are normally present but held in check by ‘suppressor’ immune cells, begin to destroy the body's insulin-producing beta cells. In the BB rat model of Type I diabetes cell surface expression of RT6 is a marker for suppressor cells. To date, RT6 is the only known marker in any species for immune cells that possess such suppressor activity.

Until recently, the function of RT6 protein was unknown. We have now demonstrated that RT6 belongs to a family of NAD glycohydrolase (NADase) enzymes which convert an important cellular metabolite, nicotinamide adenine dinucleotide (NAD), into adenosine diphosphoribose (ADPR) and nicotinamide (NIC). It is interesting to note that nicotinamide, one of the products of NAD catabolism by RT6, is currently in clinical trials as a potential drug to prevent human Type I diabetes.

Transplantation provides a means to treat not only the primary defect in diabetes (the absent islets of Langerhans), but also the organs damaged through secondary complications (such as the kidney). Our laboratory has demonstrated that donor specific transfusion and treatment with anti-CD40L antibody results in permanent islet allograft survival and prolonged skin allograft survival in mice. We have also observed that this system can prolong xenografts of rat tissues in mice. Our method of tolerance induction does not cause generalized immunosuppression.

Prior to clinical application of our two element protocol, the feasibility of its effectiveness is being tested in primates. Our preliminary results suggest that our approach induces permanent allograft acceptance.

Office: Biotech2 Suite 218
Phone: 508-856-3800
E-mail: Aldo.Rossini@umassmed.edu
Keywords: Autoimmunity, Cell Biology, Animal Models of Disease, Genetics, Diabetes

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